This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Over the past two years we have developed methodologies for chronic gastrointestinal dosing of drugs in monkeys and studied the relationship between dose, serum level, CSF level and central D2 occupancy for two antipsychotics. We determined that risperidone's actions in the brain are almost entirely the result of its active metabolite paliperidone. Additionally, we showed that these drugs do not exhibit the same occupancy of D2 receptors in all brain regions. We plan to follow up this exciting observation in future studies to relate regional D2 occupancy to measures of therapeutic effects and side effects.